Park Youngji, Rangel Carolina, Reynolds M Megan, Caldwell M Craig, Johns Misty, Nayak Mamatha, Welsh C Jane R, McDermott Sean, Datta Sumana
Department of Biochemistry and Biophysics, Texas A&M University, TAMU 2128, College Station, TX 77843-2128, USA.
Dev Biol. 2003 Jan 15;253(2):247-57. doi: 10.1016/s0012-1606(02)00019-2.
Mutations in the Drosophila trol gene cause cell cycle arrest of neuroblasts in the larval brain. Here, we show that trol encodes the Drosophila homolog of Perlecan and regulates neuroblast division by modulating both FGF and Hh signaling. Addition of human FGF-2 to trol mutant brains in culture rescues the trol proliferation phenotype, while addition of a MAPK inhibitor causes cell cycle arrest of the regulated neuroblasts in wildtype brains. Like FGF, Hh activates stem cell division in the larval brain in a Trol-dependent fashion. Coimmunoprecipitation studies are consistent with interactions between Trol and Hh and between mammalian Perlecan and Shh that are not competed with heparin sulfate. Finally, analyses of mutations in trol, hh, and ttv suggest that Trol affects Hh movement. These results indicate that Trol can mediate signaling through both of the FGF and Hedgehog pathways to control the onset of stem cell proliferation in the developing nervous system.
果蝇trol基因的突变会导致幼虫大脑中神经母细胞的细胞周期停滞。在此，我们表明trol编码果蝇Perlecan的同源物，并通过调节FGF和Hh信号来调控神经母细胞的分裂。在培养的trol突变体大脑中添加人FGF-2可挽救trol的增殖表型，而添加MAPK抑制剂会导致野生型大脑中受调控的神经母细胞发生细胞周期停滞。与FGF一样，Hh以Trol依赖的方式激活幼虫大脑中的干细胞分裂。免疫共沉淀研究结果与Trol和Hh之间以及哺乳动物Perlecan和Shh之间的相互作用一致，且这些相互作用不受硫酸乙酰肝素的竞争影响。最后，对trol、hh和ttv突变的分析表明，Trol会影响Hh的移动。这些结果表明，Trol可通过FGF和Hedgehog两条信号通路来介导信号传导，从而控制发育中神经系统中干细胞增殖的起始。
